Reduction of inflammatory response in the mouse brain with adenoviral-mediated transforming growth factor-β1 expression
In: Stroke (1970), Jg. 32 (2001), Heft 2, S. 544-552
Online
academicJournal
- print, 54 ref
Zugriff:
Background and Purpose-Chemokines have been shown to play an important role in leukocyte and monocyte/macrophage infiltration into ischemic regions. The purpose of this study is to identify whether overexpression of the active human transforming growth factor-β1 (ahTGF-β1) can downregulate expression of monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), and intercellular adhesion molecule- 1 (ICAM-1) and reduce ischemic brain injury. Methods-Overexpression of transforming growth factor-β1 (TGF-β1) was achieved through adenoviral gene transfer. Five days after adenoviral transduction, the mouse underwent 30 minutes of middle cerebral artery occlusion followed by 1 to 7 days of reperfusion. TGF-β1, MCP-1, MIP-1α, and ICAM-1 were detected by enzyme-linked immunosorbent assay and immunohistochemistry. Infarct areas and volumes were measured by cresyl violet staining. Results-MCP-1 and MIP-la expression is increased after middle cerebral artery occlusion, and double-labeled immunostaining revealed that MCP-1 is colocalized with neurons and astrocytes. Viral-mediated TGF-β1 overexpression was significantly greater at measured time points, with a peak at 7 to 9 days. The expression of MCP- 1 and MIP- 1α, but not ICAM-1, was reduced in the mice overexpressing ahTGF-β1 (P<0.05). Furthermore, infarct volume was significantly reduced in the mice overexpressing ahTGF-β1 (P<0.05). Conclusions-This study demonstrates that MCP-1 and MIP-1α expressed in the ischemic region may play an important role in attracting inflammatory cells. The reduction of MCP- 1 and MIP-1α, but not ICAM-1, in the mice overexpressing ahTGF-β1 suggests that the neuroprotective effect of TGF-β1 may result from the inhibition of chemokines during cerebral ischemia and reperfusion.
Titel: |
Reduction of inflammatory response in the mouse brain with adenoviral-mediated transforming growth factor-β1 expression
|
---|---|
Autor/in / Beteiligte Person: | LI, PANG ; WEN, YE ; CHE, Xiao-Ming ; ROESSLER, Blake J ; BETZ, A. Louis ; YANG, Guo-Yuan |
Link: | |
Zeitschrift: | Stroke (1970), Jg. 32 (2001), Heft 2, S. 544-552 |
Veröffentlichung: | Hagerstown, MD: Lippincott Williams & Wilkins, 2001 |
Medientyp: | academicJournal |
Umfang: | print, 54 ref |
ISSN: | 0039-2499 (print) |
Schlagwort: |
|
Sonstiges: |
|